Petropoulou Chariklia, Kotantaki Panorea, Karamitros Dimitris, Taraviras Stavros
Department of Pharmacology, Medical School, University of Patras, 26500 Rio, Patras, Greece.
Front Biosci. 2008 May 1;13:4485-94. doi: 10.2741/3018.
Cdt1 and its inhibitor Geminin are important regulators of replication licensing. In normal cells, a critical balance between these two proteins ensures that firing of each origin along the genome will take place only once per cell cycle. Cdt1 overexpression in cell lines and animals leads to aberrant replication, activates DNA damage checkpoints and predisposes for malignant transformation. Geminin inactivation mimics the effects of Cdt1 overexpression in cells and generates mitotic defects and abnormal chromosome segregation. Aberrant expression of Cdt1 and Geminin is thus linked to DNA replication defects, aneuploidy and genomic instability. These traits are considered integral to precancerous states and essential elements for malignant transformation. Moreover, Cdt1 and Geminin expression is deregulated in human tumor specimens and Cdt1 and Geminin may represent novel markers useful for cancer diagnosis and prognosis.
Cdt1及其抑制剂Geminin是复制许可的重要调节因子。在正常细胞中，这两种蛋白质之间的关键平衡确保基因组中每个起始位点在每个细胞周期仅启动一次。在细胞系和动物中Cdt1过表达会导致异常复制，激活DNA损伤检查点并易引发恶性转化。Geminin失活在细胞中模拟了Cdt1过表达的效应，并产生有丝分裂缺陷和异常染色体分离。因此，Cdt1和Geminin的异常表达与DNA复制缺陷、非整倍体和基因组不稳定有关。这些特征被认为是癌前状态的组成部分以及恶性转化的基本要素。此外，在人类肿瘤标本中Cdt1和Geminin的表达失调，Cdt1和Geminin可能代表可用于癌症诊断和预后的新型标志物。
